What is the main cause of increased Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels?

Main Causes of Elevated ALT and AST Levels

The most common causes of elevated ALT and AST levels are nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease. 1

Hepatocellular Pattern of Liver Injury

Elevations in ALT and AST indicate a hepatocellular pattern of liver injury, which is directly linked to hepatocyte damage. The causes can be categorized as follows:

Common Causes

• Nonalcoholic fatty liver disease (NAFLD)

  • Most common liver disease in developed countries
  • Prevalence of 20-30% in general population
  • Increases to 70% in obesity and 90% in diabetes mellitus 1
  • AST:ALT ratio typically <1

• Alcohol-induced liver disease

  • AST:ALT ratio generally >2 1, 2
  • Present in approximately 75% of habitual drinkers 2

Less Common Causes

• Drug-induced liver injury
• Viral hepatitis (hepatitis B and C)
• Hereditary hemochromatosis 1, 3

Rare Causes

• Alpha1-antitrypsin deficiency
• Autoimmune hepatitis
• Wilson disease 1, 3

Differentiating Features

AST:ALT Ratio

• >2: Strongly suggests alcoholic liver disease 2, 4
• <1: Typical of NAFLD and metabolic-related fatty liver 1, 2
• >1 in non-alcoholic disease: May suggest progression to cirrhosis 4

ALT:LD (Lactate Dehydrogenase) Ratio

• Can help differentiate between causes of acute liver injury:
  • Viral hepatitis: Mean ALT/LD ratio of 4.65
  • Ischemic hepatitis: Mean ALT/LD ratio of 0.87
  • Acetaminophen injury: Mean ALT/LD ratio of 1.46 5

Non-Hepatic Causes of Elevated Transaminases

It's important to note that AST is not liver-specific and can be elevated due to:

• Cardiac muscle injury (myocardial infarction)
• Skeletal muscle disorders (polymyositis, acute muscle injury)
• Hemolysis
• Thyroid disorders
• Celiac disease 6, 7, 3

Evaluation Approach

For patients with elevated ALT and AST, initial evaluation should include:

1. Assessment for metabolic syndrome and insulin resistance:

   • Waist circumference
   • Blood pressure
   • Fasting lipid levels
   • Fasting glucose or A1C levels 3

2. Laboratory tests:

   • Complete blood count with platelets
   • Serum albumin, iron, total iron-binding capacity, and ferritin
   • Hepatitis C antibody and hepatitis B surface antigen testing 3
   • Liver synthesis markers (albumin, prothrombin time, INR) 2

3. Non-invasive fibrosis assessment:

   • FIB-4 score
   • NAFLD fibrosis score 2, 3

Common Pitfalls to Avoid

• Overlooking non-hepatic causes of enzyme elevation
• Assuming normal enzymes exclude significant liver disease - normal ALT/AST does not rule out chronic hepatitis or cirrhosis
• Focusing solely on ALT/AST without considering patterns of liver injury
• Prematurely discontinuing medications for mild, asymptomatic elevations without proper evaluation 2

Management Considerations

• For suspected NAFLD with mild elevations, a trial of lifestyle modifications is appropriate:

  • Mediterranean diet
  • Regular exercise
  • Weight loss if overweight or obese 2

• Referral to hepatology is recommended for:

  • Persistent elevation >6 months despite interventions
  • ALT elevation >5× ULN
  • Elevated bilirubin with elevated transaminases
  • Signs of hepatic decompensation 2